The Molecular Mechanism of Metabolic Remodeling in Lung Cancer

Abstract

Metabolic remodeling is a key phenomenon in the occurrence and development of tumors. It not only offers materials and energy for the survival and proliferation of tumor cells, but also protects tumor cells so that they may survive, proliferate and transfer in the harsh microenvironment. This paper attempts to reveal the role of abnormal metabolism in the development of lung cancer by considering the processes of glycolysis and lipid metabolism, Identification of the molecules that are specifically used in the processes of glycolysis and lipid metabolism, and their underlying molecular mechanisms, is of great clinical and theoretical significance. We will focus on the recent progress in elucidating the molecular mechanism of metabolic remodeling in lung cancer.

Keywords: Glycolysis; Lipid metabolism; Lung cancer; Molecular mechanism.

Figure 1

Metabolic Remodeling in lung cancer. Lung cancer cells consume large amounts of glucose via GLUTs and convert glucose to G6P, which involves in PPP metabolism and produced genetic substances, cytoskeleton and functional proteins. Pyruvate, a production by glucose, offers lactate for microenvironment and citrate for glycolsis. Lactate is excreted and absorbed through MCTs, and this phenomenon is known as lactic acid shuttle system. Citrate cannot participate in metabolism smoothly due to ROS inhibits a key enzyme (aconitase) activity in TCA. However, citrate participates in endogenous fatty acids metabolism. Some citrate is converted to malate and continues to participate in TCA. As a result, endogenous fatty acids metabolism offers lung cancer cells the energy for proliferation and invasion, and is regulated by three key regulatory enzyme, which are negatively regulated by SREBPs. G6P Glucose-6-Phosphate), MCTs (Monocarboxylate transporters), ROS (Reactive oxygen species),

Figure 2

Related molecular mechanisms of metabolic remodeling in lung cancer. PI3K/AKT/mTOR and MEK/ERK/AMPK signaling pathways are both involved in metabolic remodeling of lung cancer cells. And, the two signaling pathways are regulated by extracellular signals (e.g. GFs, hormones, cytokines) to activate cascade response. Importantly, the interaction of the two signaling pathways affects glycolysis, TCA cycle, PPP, endogenous fatty acids metabolism. Consequently, the aggressive biological behaviors of lung cancer cells are activated by metabolic remodeling.

Figure 3

Regulatory factors of metabolic remodeling in lung cancer. Metabolic remodeling in lung cancer include glycolysis metabolism and endogenous fatty acids metabolism. Many negative/ positive regulatory factors involved in glycolysis and endogenous fatty acids metabolism.